Cellular reprogramming has emerged in recent years as a promising approach in regenerative medicine whereby abundant adult cells ofthe body are converted into medically important cell types to repair tissues lost due to disease or injury. This approach could prove valuable for developing treatments for Type 1 diabetes, a disease that results from autoimmune destruction of insulin secreting beta cells. The long term goal of this proposal is to understand the cellular and molecular mechanisms that control beta cell reprogramming. We will take advantage of a recently developed model system where a small number of transcription factors reprogram adult exocrine cells into beta cells. In Specific Aim I, we will determine the functional contribution of each reprogramming factor to the beta cell reprogramming process. In Aim II, we will determine the functional and physical interactions between reprogramming factors and chromatin remodeling genes. In Aim III, we will determine whether exocrine identity genes act as molecular barriers to beta cell reprogramming. The proposed studies are expected to shed important light on the molecular mechanisms that control beta cell reprogramming. Such molecular insights will allow better control ofthe reprogramming process and aid the development of novel cell replacement therapies to treat Type 1 diabetes.